Developmental toxicology of cadmium in living embryos of a stable transgenic zebrafish line.

Developmental toxicology of cadmium in living embryos of a stable transgenic zebrafish line.
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DOI:
10.1289/ehp.021101041
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发表时间:
2002-10
影响因子:
10.4
通讯作者:
Krone PH
Krone PH
中科院分区:
环境科学与生态学1区
文献类型:
--
作者:
Blechinger SR;Warren JT Jr;Kuwada JY;Krone PH

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镉和其他重金属的毒性作用已得到充分证实,许多这些和其他环境污染物已知具有胚胎毒性或致畸性。然而,已经证明难以在完整动物的广泛细胞群中鉴定对毒物有反应的单个细胞,特别是在细胞分化时不断改变其分子和生理特征的早期发育期间。在这里,我们报告了一个体内系统的建立,使用热休克蛋白70基因激活作为衡量镉毒性的转基因斑马鱼携带稳定整合的热休克蛋白70增强的绿色荧光蛋白(eGFP)报告基因的早期幼虫。我们证明,eGFP表达在这株鱼作为一个准确的和可重复的指示细胞特异性诱导热休克蛋白70基因表达。此外,转基因响应剂量依赖性的方式在浓度类似于观察到的形态指标的早期生命阶段的毒性,是足够敏感的检测镉的剂量低于中位联合不良反应浓度和中位致死浓度。该转基因品系的稳定性质应允许在整个发育过程中对胚胎和幼虫进行极其快速和可重现的毒理学分析。
The toxic effects of cadmium and other heavy metals have been well established, and many of these and other environmental pollutants are known to be embryotoxic or teratogenic. However, it has proven difficult to identify individual cells that respond to toxicants among the wide range of cell populations in an intact animal, particularly during early development when cells are continually changing their molecular and physiologic characteristics as they differentiate. Here we report the establishment of an in vivo system that uses hsp70 gene activation as a measure of cadmium toxicity in living early larvae of transgenic zebrafish carrying a stably integrated hsp70-enhanced green fluorescent protein (eGFP) reporter gene. We demonstrate that eGFP expression in this strain of fish acts as an accurate and reproducible indicator of cell-specific induction of hsp70 gene expression. Furthermore, the transgene responds in a dose-dependent manner at concentrations similar to those observed for morphologic indicators of early-life-stage toxicity and is sensitive enough to detect cadmium at doses below the median combined adverse effect concentration and the median lethal concentration. The stable nature of this transgenic line should allow for extremely rapid and reproducible toxicologic profiling of embryos and larvae throughout development.
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发表时间: 2002-03-01
影响因子: 2.6
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发表时间: 1986-01-01
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作者:
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